FKBPL

Chr 6

FKBP prolyl isomerase like

Also known as: DIR1, NG7, WISP39

NCBI Gene: 63943ENSG00000204315UniProt: Q9UIM3

The protein encoded by this gene has similarity to the immunophilin protein family, which play a role in immunoregulation and basic cellular processes involving protein folding and trafficking. The encoded protein is thought to have a potential role in the induced radioresistance. Also it appears to have some involvement in the control of the cell cycle. [provided by RefSeq, Jul 2008]

51
ClinVar variants
5
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— FKBPL
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
5 Pathogenic / Likely Pathogenic· 37 VUS of 51 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.62LOEUF
pLI 0.000
Z-score -0.23
OE 1.07 (0.71–1.62)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.42Z-score
OE missense 0.71 (0.62–0.82)
136 obs / 191.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.1.07 (0.71–1.62)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.71 (0.62–0.82)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.73
0≤1.21.6
LoF obs/exp: 15 / 14.1Missense obs/exp: 136 / 191.2Syn Z: 1.84

ClinVar Variant Classifications

51 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic4
Likely Pathogenic1
VUS37
Likely Benign7
Benign2
4
Pathogenic
1
Likely Pathogenic
37
VUS
7
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
4
0
4
Likely Pathogenic
0
0
1
0
1
VUS
0
32
5
0
37
Likely Benign
0
3
2
2
7
Benign
0
2
0
0
2
Total03712251

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

FKBPL · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Proteome-wide Mendelian randomization identifies therapeutic targets for ankylosing spondylitis.
Zhao W et al.·Front Immunol
2024
The therapeutic and diagnostic potential of FKBPL; a novel anticancer protein.
Robson T et al.·Drug Discov Today
2012Review
FKBPL: a marker of good prognosis in breast cancer.
Nelson L et al.·Oncotarget
2015Meta-analysis
A placenta-on-a-chip model to determine the regulation of FKBPL and galectin-3 in preeclampsia.
Ghorbanpour SM et al.·Cell Mol Life Sci
2023Functional
FKBPL is a critical antiangiogenic regulator of developmental and pathological angiogenesis.
Yakkundi A et al.·Arterioscler Thromb Vasc Biol
2015
Loss of Expression of Antiangiogenic Protein FKBPL in Endometrioid Endometrial Carcinoma: Implications for Clinical Practice.
Obradović DD et al.·Medicina (Kaunas)
2022
FKBPL-based peptide, ALM201, targets angiogenesis and cancer stem cells in ovarian cancer.
Annett S et al.·Br J Cancer
2020
FKBPL and its peptide derivatives inhibit endocrine therapy resistant cancer stem cells and breast cancer metastasis by downregulating DLL4 and Notch4.
McClements L et al.·BMC Cancer
2019
Proteome-wide Mendelian randomization and colocalization analysis identify therapeutic targets for stroke.
Zhao X et al.·BMC Neurol
2025
Identification of prospective novel drug targets for immune thrombocytopenia by integrating plasma proteome.
He W et al.·Hematology
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools